Determination of Norfloxacin Free Interstitial Levels in Skeletal Muscle by Microdialysis

Abstract

Tissue penetration and distribution of antibiotics are important issues when establishing antibiotic therapies. Free concentrations of antibiotics at the infection site are responsible for bacteria killing effect. The knowledge of the correlation between blood levels and tissue concentrations can be helpful for adequate dosing of these drugs. It was the aim of this study to investigate norfloxacin pharmacokinetics in rats to predict free interstitial levels of the drug, determined by microdialysis, using pharmacokinetic parameters derived from total plasma data. Norfloxacin free tissue and total plasma levels were determined in Wistar rats after administering 5 and 10 mg/kg i.v. bolus doses. Plasma and microdialysis samples were analyzed by high‐performance liquid chromatography. Norfloxacin plasma pharmacokinetics was consistent with a two compartments model. A simultaneous fitting of plasma and tissue concentrations was performed using a proportionality factor because norfloxacin free tissue levels determined by microdialysis were lower than those predicted using plasma data. A similar proportionality (fT) factor was calculated by the computer program Scientist® for both doses (0.25 ± 0.08). It can be concluded that it is possible to predict concentration time profiles of norfloxacin in the peripheral compartment based on plasma data using the adequate tissue penetration factor. © 2002 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2433–2440, 2002